NASDAQ: CLSN. July 2015

Transcription

1 NASDAQ: CLSN July

2 Safe Harbor Statement Except for historical information, the statements made in this presentation are forward-looking statements involving significant risks and uncertainties. These risks and uncertainties, including those related to the future financial position and business strategy of the Company, are detailed in the Company s filings with the Securities and Exchange Commission. 2

3 A Fully Integrated Oncology Company Deep Pipeline and Multiple Technology Platforms Chemotherapy, Immunotherapy and RNA Therapy Platforms Multiple near term opportunities for value creation Phase 3 in Primary Liver Cancer (HCC) Phase 2 in RCW Breast Cancer Phase 1 in Ovarian Cancer Pre-Clinical/Phase 1 in GBM Brain Cancer Pre-Clinical Research for RNA Lung Specific Delivery Discovery assets complement proven development capabilities Nanoparticle Technology 1 st Line Therapies Oncology Focused Strong cash position following EGEN acquisition 3

4 Three Platforms to Drive Growth LTSL TheraPlas TheraSilence Lysolipid Thermally Sensitive Liposomes DNA-based Non-viral Immunotherapy RNA-based Non-viral Carriers, Lung Specific ThermoDox: Liposomal Doxorubicin Phase 3 Study in HCC Phase 2 Study in RCW GEN-1: IL-12 Immunotherapy Phase 1 in Ovarian Cancer Pre-Clinical/Phase 1 in GBM GEN-2: Delivery of sirna, mrna, Pre-Clinical Delivery Cancer Pre-Clinical Delivery PAH, ++ 4

5 Pipeline of Targeted Therapeutic Agents INDICATION PRODUCT CANDIDATE PRE-CLINICAL PHASE 1-2 PHASE 3 Primary Liver ThermoDox /OPTIMA Study Phase III enrolling RCW Breast Ovarian Glioblastoma ThermoDox/US & Euro-DIGNITY GEN-1/Multiple Studies GEN-1 Phase II enrolling Phase I enrolling Pre-Clin. Efficacy/Safety/Toxicology Lung Disease GEN-2/TheraSilence Efficacy/Safety/Tox Key Near-Term Milestones: ASCO abstract from GOG (GEN-1+Doxil) Ovarian Cancer Trial Translational Data from GOG (GEN-1+Doxil) Ovarian Cancer Trial Initiation of GEN-1 Phase 1b Neo-Adjuvant Ovarian Cancer Trial Updated OS Data from HEAT Study PoC Preclinical Data for GEN-1+SoC in GBM Brain Cancer 5

6 LTSL Platform ThermoDox 6

7 Hepatocellular Carcinoma Large and Deadly Global Cancer 5 th most prevalent 800,000 annual incidence worldwide; growing 5% per year By 2020, expected to be the #1 cancer, surpassing lung cancer China has 50% of new cases; 75% in Asia 4 th highest mortality 5-year survival rate less than 10% Median survival from time of diagnosis is less than 3 years Cure, usually through surgery, is possible in less than 20% of patients Local therapies include: RFA, TACE and radiation RFA is the dominant treatment average local recurrence rate of 50% for lesions > 3 cm ThermoDox + RFA addresses limitations of current standard of care by Expanding the Treatment Zone 7

8 RF Liver Ablation + ThermoDox Expanding the Treatment Zone Addresses RFA Limitations ThermoDox + RFA misses micrometastases outside ablation zone ThermoDox Ablation Zone Ablation Thermal Zone RFA Electrode ThermoDox infused IV ~15 minutes prior to srfa ThermoDox concentrates in the Thermal Zone over a 45 minute period Doxorubicin is released in the Thermal Zone expanding treatment area 8

9 Learnings from HEAT Study Advanced Understanding of RFA and HCC Treatment Data from 285 Patient Subgroup Reviewed at Multiple International Medical Conferences RFA must be used within its engineered design limitations 3 cm or greater lesions require multiple overlapping ablations Longer RFA time (> 45 minutes) result in better outcomes Heating duration directly affects clinical outcome by allowing for high local perfusion of drug at the tumor site High tissue concentration of ThermoDox prevents recurrence Supported by Multivariate Cox Regression Analysis PFS is not a reliable endpoint in HCC trials 9

10 Survival Probability Sub-Group Analysis of HEAT Study Data 285 Patients with Standardized RFA (>45 minutes) 1 OVERALL SURVIVAL Chart Legend srfa plus ThermoDox srfa alone Months Overall Survival as of 1/15/2015 HR=0.628 (95% Cl ) P Value = 0.02 Standardized RFA > 45 mins. 10

11 Sub-Group Analysis (Single Lesion) of HEAT Study 285 Patients Standardized RFA >45 minutes +/- ThermoDox vs 167 Patients RFA < 45 minutes Survival Probability 1 OVERALL SURVIVAL as of 1/15/ Chart Legend RFA > 45min. plus ThermoDox RFA > 45min. Alone (no ThermoDox) RFA < 45mins. (with and without ThermoDox) Months OS srfa > 45mins. +/- ThermoDox HR=0.628 (95% Cl ) P Value=0.02 Standardized RFA > 45 mins. 11

12 Phase 3 OPTIMA Study Design ThermoDox Plus srfa* General Eligibility Non-resectable HCC Single lesions Lesion > 3 cm but not > 7 cm Treatment naïve Child-Pugh A Stratification Lesion size: 3-5 cm / 5-7 cm Geography Randomize 1:1 N=275 N=275 ThermoDox plus srfa* Dummy Infusion + srfa* Primary Endpoint Overall Survival (OS) Secondary Endpoints Progression Free Survival; Safety First Patient Enrolled Q Interim Efficacy Analysis 118 OS Events / HR < OS Events / HR < 0.70 ~75 Clinical Sites in 13 Countries Final Efficacy 197 OS Events / HR < 0.75 * Standardized Radiofrequency Ablation > 45 minutes 12

13 Recurrent Chest Wall Breast Cancer Very Difficult with Severe Complications Breast cancer recurring in the chest wall affects ~35,000 post-mastectomy patients in the US and Europe annually Up to 40% of women undergoing a mastectomy as primary treatment will experience local recurrence Reappearance of cancer in the ipsilateral breast or the chest wall Patients have ulceration, bleeding and pain, highly debilitating and visible cancer Local tumor control is a primary objective in treating these patients 13

14 Subjects Phase 2 RCW Breast Cancer Study ThermoDox + Hyperthermia Phase 2 DIGNITY Study Primary Objectives Limited Treatment Options Complete Response Evaluate local-regional breast tumor response in patients undergoing ThermoDox + hyperthermia; 17 patients enrolled & treated, 13 evaluable for efficacy All patients experienced stabilization of disease 70% of patients in evaluable population observed local responses - 5 CRs & 4 PRs Establish pharmacokinetic bioequivalence between ThermoDox manufactured at two different manufacturing sites Combined Phase 1 Data (n = 29) Progressive Disease Partial Response Stable Disease Complete Response Local Response 48.3% Dose (mg/m 2 ) 14Slide 14

15 Euro-DIGNITY Study ThermoDox + Hyperthermia + Radiation Primary Objectives Evaluate complete and partial response after 3 cycles of ThermoDox + Hyperthermia & Radiation Treatment (Tri-Modal Therapy) Evaluate loco-regional breast tumor control in patients undergoing Tri-Modal Therapy 100 patients to be enrolled aa Open Label Design a Study Timelines Site Activation: Q Recruitment Period: Q LP/LV through Follow-Up: Slide 15

16 Early Access Program (EAP) in Europe ThermoDox for RCW Breast Cancer Patients EAP offers patients access to innovative non-registered pharmaceuticals EAP (Specials Market) in Europe is over $6B per year License/Distribution Agreement signed with mytomorrows in Jan 2015 May be provided to patient with a life threatening or debilitating disease and no alternative therapy exists EAP Requirements Product must be in Phase 2 trials or later; have shown evidence of efficacy and in an active program for registration Awareness and physician training are used to educate the medical community EAP Pricing/Market Product pricing determined by the Sponsor; Equivalent to registered products Partnered with mytomorrows RCW breast cancer in EU is ~25,000 patients annually 35 to 40 Centers of Excellence in EU that treat patients with RCW breast cancer using Thermal Therapy 16Slide 16

17 TheraPlas Platform GEN-1 17

18 Protein Levels GEN-1 Novel PPC Plasmid DNA Nanoparticle Rationale for Local Therapy with DNA Nanoparticles Local production of potent cytokine IL-12 Recruits immune system, multiple mechanisms, effective in multiple cancer types Avoids serious toxicities and poor pk of recombinant IL-12 GEN-1 an Alternative to ril-12 Poor pk For Distinct IL-12 Action Mechanisms ril-12 Toxic Level GEN-1 Therapeutic Level 18

19 Cytokines (mg/ml) GEN-1 Clinical Experience To-Date 1 Convincing Evidence of 2 Biological Activity 30 Peritoneal Fluid Plasma Single Agent Benefit Low Doses High Doses All Doses IFN-g TNF-a GEN-1 (DNA mg/m 2 ) 0 Median Survival Months 3 Lack of Overlapping Toxicities Allows for Combination Therapies GEN-1 (IP) Gastrointestinal Low Grade Fever Chills Catheter Site Pain/Redness Abdominal Discomfort Chemotherapy (IP) Cardiovascular, Hematological Metabolic, Neurologic Fever, Infection Urinary Problems, Gastrointestinal Hepatic, Fatigue, Metabolic, Pain 19

20 IL-12: A Powerful Immune Modulating Agent with Multiple Mechanisms of Action 1. NK Cell Activation 2. T Cell Activation Mechanisms of Action 3. Anti-angiogenesis 4. T Reg suppression

21 Ovarian Cancer Large and Deadly Global Cancer 8 th most diagnosed cancer among women 225,000 annual incidence worldwide 22,000 in US and 100,000 in developed countries 5 th highest mortality among women 5-year survival rate for all stages is 45%; Survival rate reduces dramatically if not localized cancer 15% diagnosed with localized cancer, eligible for potentially curative surgery Local therapies for ovarian cancer Ovarian cancer is not diagnosed early - spreads to regional/mets requiring combo regimens Most common site of recurrence in abdomen importance of intra-peritoneal administered therapy GEN-1 administered IP; ideal adjuvant to SoC therapy Sources: Cancer Statistics, American Cancer Society; Globocan; SEER database 21

22 GEN-1 for Ovarian Cancer Local Immunotherapy Addresses Limitations of Chemotherapy Persistent Local Delivery of an Immune Agent with a Single Administration PPC Delivery System (PEG-PEI-Chol) IL-12 Plasmid GEN-1 Stable Nanoparticles for Local Delivery Peritoneal Mets GEN-1causes the production of IL-12 at cancer site IL-12 addresses cancer cells that are chemo-resistant by recruiting the immune system, inducing powerful anticancer mechanisms Clinical experience strongly supports development in combination with first line treatment 22

23 Phase Ib Trial: GEN-1 + Doxil Platinum Resistant Ovarian Cancer Safety, Biological Activity & Efficacy of Combination Therapy Traditional 3+3 Escalation Design (n=16; enrollment completed) Dose Level GEN-1 (mg/m 2 ) Doxil (mg/m 2 ) Status Completed Completed Completed All doses well tolerated; no DLTs Better clinical responses at 36 mg/m 2 dose Clinical Response Rate (SD+PR+CR) (all doses): > 50% Clinical Response Rate (SD+PR+CR) at 36 mg/m 2 dose: 86% Compares favorably to current SoC in Platinum Resistant Ovarian Cancer Single Agent Doxil in four (4) previous studies: 45-50% Overall CRR 23

24 GEN-1 as a First Line Treatment in Ovarian Cancer Phase I Study Newly Diagnosed Ovarian Cancer Not Surgical Candidate Traditional 3+3 Dose Escalation Standard Neoadjuvant Chemotherapy with 9 weekly cycles of GEN-1 Debulk - Surgery Neoadjuvant Study in Newly Diagnosed Ovarian Cancer Patients To determine safety, dose, and feasibility in target patient population Primary Endpoint Optimal Dose (Max or MTD) Secondary Endpoints pcr, PFS, IFN, IL-12, VEGF 24

25 Grams Percentatge GEN-1 + Avastin in Disseminated Ovarian Cancer Pre-Clinical Study Dramatic Improvement in Avastin Activity in Combination with pmil-12/ppc (GEN-1) (Study 1) Tumor Burden Tumor Incidence Untreated Control mil-12/ppc Avastin Avastin + mil- 12/PPC Untreated Control mil-12/ppc Avastin Avastin + mil-12/ppc DAY mil-12/ppc GEN-1 Avastin 25

26 Tumor Weight (mg) GEN-1 + Avastin in Disseminated Ovarian Cancer Second Pre-Clinical Study Dramatic Improvement in Avastin Activity in Combination with pmil-12/ppc (GEN-1) Control pmil-12/ppc Avastin (low, med, high) pmil-12/ppc + Avastin (low/med/high) Comparison # Mean Tumor Burden Two-Tailed P-Value Avastin +GEN-1 vs. Control mg 80.1 mg GEN-1 plus Avastin Avastin+GEN-1 vs. Avastin mg 48.9 mg L M H L M H Human ovarian cancer cells were implanted IP. Avastin treatment at 5 mg/kg (low), 10 mg/kg (medium) and 20 mg/kg (high) was initiated 9 days after tumor implantation pmil-12/ppc was given weekly for 4 weeks; 14 days after tumor implantation Avastin+GEN-1 vs. GEN mg 41.6 mg

27 Proposed Phase I/II in Platinum Resistant Ovarian Cancer GEN-1with Avastin + Doxil, the SoC Inhibition of VEGF synthesis by IL-12 through the interferon-gamma (IFN-gamma) pathway helps explain the remarkable synergy between GEN-1 and Avastin Potentially addresses the VEGF escape mechanism described in resistance to Avastin therapy Previous clinical studies have shown excellent safety of GEN-1with Doxil in this patient population Phase 1 design to optimize GEN-1and Avastin dosing to enhance safety profile and establish efficacy Initiate trial in late 2015/early

28 GEN-1 with Avastin and Doxil Platinum Resistant Recurrent Ovarian Cancer Platinum Resistant Recurrent Ovarian Cancer Standard 3x3 Dose Escalating Design 1 ST Cohort N= Day Cycle Day 1: Dox + Avastin + GEN-1 Day 8: GEN-1 Day 15: Avastin + GEN-1 Day 22: GEN-1 DSMB Primary Endpoint Secondary Endpoint Secondary Endpoint (Biological/Immunological) Optimal Safe Dose (Max or MTD) Clinical Objective Tumor Response (RECIST) IL-12, IFN-γ, TNF-α, IL-10, TGF-β, and VEGF concentrations in the blood and peritoneal fluid 28

29 Glioblastoma Multiform Planned Phase 1 in 2 nd Half of 2015 Preclinical Experience Survival Benefits in Glioma Model IL-12 expression for one month in normal brain tissue Mechanism for local administration Bio-distribution studies Safety established Single intracranial injection 20 Brain tumor Intra-Cranial Administration Post-Resection Untreated BCNU GEN-1 GEN-1+BCNU Treatment Days 29

30 TheraSilence Platform Lung-Specific Delivery of RNA Therapeutics 30

31 Anti-miR-145 (pmol/g tissue) Transcripts (per untreated) TheraSilence Systemic RNA Delivery to the Lung Staramine and Polymeric Systems Unique Lung Delivery - Independent of RNA Type mrna pre-clinical program in NHP and murine models sirna pre-clinical PAH and other pulminary diseases sirna Lung Liver * p<0.02 Intra-Venous Delivery of Luciferase mrna 40 0 Anti-miRNA h 48 h Ventricle 0 Lung Lt Rt Celsion BD15k Nano-Particle 31

32 Tissue Luciferase Expression Levels Non-Human Primate Study TheraSilence - BD15 1.0E E E E E+04 * 1 mg/kg 2 mg/kg PRIMARILY LUNG EXPRESSION 0.0E+00 Lung Spleen Liver *Average of 4 samples 8.0E+06 LDF 6.0E E E E+00 * Lung Spleen Liver PRIMARILY LIVER/SPLEEN EXPRESSION 32

33 Strong Patent and Regulatory Protection Chemotherapy Delivery LTSL Platform CoM Patent (2021) Method Patent (2026) Orphan Drug Designation for HCC U.S. 7 year exclusivity Europe 10 year exclusivity Eligible for 5 year Hatch-Waxman (2031) DNA Delivery TheraPlas CoM Patent (2027) Eligible for Orphan Designation for Ovarian and GBM U.S. 7 year exclusivity RNA Delivery TheraSilence CoM Patent (2031) Delivery of RNAi, sirna and mirna Cell derived RNA + Delivery CoM Patent (2030) Proprietary RNA + Delivery System 33 33

34 2015 Goals First Half ThermoDox Early Access Program in Europe for RCW Breast Cancer GEN-1 Development Overview & FDA Acceptance of Neoadjuvant Ovarian Study Latest OS Sweep for HEAT Study Subgroup HR = 0.629; Pvalue= 0.02 TheraSilence Non-Human Primate Data Final Clinical Data from GEN-1 Phase 1b GOG Ovarian Study (ASCO) Translational Data from Phase 1b Ovarian Study (GEN-1 + Doxil) Second Half Initiate Patient Enrollment: ThermoDox Euro-DIGNITY Study GEN-1 Pre-Clinical Efficacy Data in GBM Initiate Patient Enrollment: GEN-1 Neoadjuvant Ovarian Study Collaboration Agreement(s) for TheraSilence RNA Delivery Initiate Patient Enrollment: GEN-1 + SOC Phase 1/2 GBM Study Initiate Patient Enrollment: GEN-1 + Doxil + Avastin Ovarian Study Final Clinical Data from ThermoDox Phase 2 US DIGNITY Study (San Antonio Breast) ~25% of Patients Enrolled in Phase III OPTIMA Study for HCC 34

35 Financial Overview Cash & Investments (3/31/15) At-The-Market RD Offering (5/2015) Estimated cash usage per month Market Capitalization Common shares outstanding Fully diluted shares outstanding Avg Daily Trading Volume $30.1 million $8.0 million ~$1.6 million $60 million 23 million 31 million ~ 275,000 35

36 Corporate Information Celsion Corporation 997 Lenox Drive Suite 100 Lawrenceville, NJ P F NASDAQ: CLSN 36